Key messages
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Tranexamic acid given as a preventive treatment makes little to no difference to heavy bleeding after vaginal birth.
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We are uncertain about whether there are any harmful effects from tranexamic acid.
What is the issue?
Postpartum haemorrhage, which is heavy bleeding after giving birth, is a common and potentially life-threatening complication of birthing a child. Most women receive drugs (called uterotonics) that stimulate the womb to contract after a normal (vaginal) delivery to prevent postpartum haemorrhage. Tranexamic acid (TXA) is a medication that is used to decrease blood loss in surgery and health conditions associated with increased bleeding. It works by helping to prevent the breakdown of blood clots. If a woman is bleeding heavily after birth, it decreases blood loss. We do not know if TXA can help prevent heavy bleeding after vaginal birth.
What did we want to find out?
We wanted to know whether fewer women have heavy bleeding after a vaginal birth if they receive TXA, with or without additional uterotonics, during vaginal birth. We also wanted to find out if taking TXA during vaginal birth was associated with any harmful effects.
What did we do?
We searched for and selected all the studies that addressed our question. We used a checklist to make sure we only included studies with information we could verify. We made judgements about the quality of the studies before comparing and summarising the results of the studies. Lastly, we rated our confidence in the findings.
Why is this important?
It is important to determine whether TXA is effective in preventing heavy bleeding after birth when given to women during vaginal birth. If there is a benefit, it could help women around the world and even play a role in reducing the number of women who die after giving birth.
How up to date is this evidence?
We searched for all available evidence up to 6 September 2024.
What evidence did we find?
We identified three studies that investigated the effects of preventive TXA. The three studies involved a total of 18,974 participants at low or high risk of heavy bleeding. Participants were given either intravenous (into a vein) TXA plus standard care or placebo (saline) injection plus standard care.
We found that preventive TXA results in little to no difference in heavy bleeding after birth.
We are very uncertain about the effect of TXA on maternal death. TXA likely makes no difference to the risk of women developing serious illness.
We found that TXA has no effect on the likelihood of receiving a blood transfusion. TXA may result in no difference in the need for further surgical intervention after giving birth. We are very uncertain about the effect of TXA on blood clots. In women with anaemia, TXA makes no difference to the need for additional drugs to help the womb contract, but in women with no anaemia, there was a slight reduction in this outcome. We are very uncertain about the effect of TXA on hysterectomy (an operation to remove the womb). There does not seem to be a difference in maternal satisfaction.
What are the limitations of the evidence?
The studies included women in both high- and low-resource settings. Few women experienced harmful effects. However, we cannot be certain that this is indeed the case in the real world.
What does this mean?
We found no difference in the number of women experiencing heavy bleeding after birth after they were given TXA preventatively during vaginal birth, and we are very uncertain about the effect of TXA on blood clots and other serious side effects. As these are harmful effects, clinicians should take into account the lack of benefit and the potential harms when considering giving routine TXA to women during vaginal birth.
Further research should focus on other interventions that may help to prevent heavy bleeding after vaginal birth.
Adding prophylactic TXA to standard care of women during vaginal birth makes little to no difference to blood loss ≥ 500 mL and likely makes little to no difference to blood loss ≥ 1000 mL or the risk of severe morbidity, compared to placebo and standard care.
TXA may result in little to no difference in additional surgical interventions to control PPH and results in little to no difference in blood transfusions. One trial found that TXA reduced the use of additional uterotonics in women without anaemia, whereas the largest trial found little to no difference in the use of additional uterotonics in women with anaemia.
Although there were very few serious adverse events reported, the evidence is insufficient to draw conclusions about the effect of TXA on maternal death, thromboembolic events, hysterectomy, or seizures.
TXA likely results in little to no difference in maternal satisfaction.
These findings are based mainly on two large trials. In the smaller of these, less than 30% of study participants were at high risk of PPH. In the largest trial, all participants had moderate to severe anaemia.
Those making decisions about routine administration of prophylactic TXA for all women having vaginal births should consider that current evidence does not show a benefit of TXA for blood loss outcomes and related morbidity, and the evidence is very uncertain about serious adverse events.
Postpartum haemorrhage (PPH) is a common and potentially life-threatening complication of labour. Several options for preventing PPH are available, but further advances in this field are important, especially the identification of safe, easy to use and cost-effective regimens. Tranexamic acid (TA), which is an antifibrinolytic agent that is used widely to prevent and treat haemorrhage, merits evaluation to assess whether it meets these criteria.
To assess the effects of TXA for preventing PPH compared to placebo or no treatment (with or without uterotonic co-treatment) in women following vaginal birth.
We searched MEDLINE, Embase, CENTRAL, and WHO ICTRP (to 6 September 2024). We also searched reference lists of retrieved studies.
All published, unpublished and ongoing randomised controlled trials (RCTs) evaluating the use of TA alone or in addition to uterotonics in the third stage of labour or during caesarean section (CS) to prevent PPH.
Two review authors independently assessed for inclusion all the potential studies identified as a result of the search strategy. We entered the data into Review Manager software and checked for accuracy.
Twelve trials involving 3285 healthy women at low risk of excessive bleeding undergoing elective CS (nine trials, 2453 participants) or spontaneous birth (three trials, 832 participants) satisfied inclusion criteria and contributed data to the analysis. All participants received routine prophylactic uterotonics in accordance with the local guideline in addition to TA or placebo or no intervention. Overall, included studies had moderate risk of bias for random sequence generation, allocation concealment, blinding, selective reporting and low risk of bias for incomplete data. The quality of evidence was also as assessed using GRADE.
Blood loss greater than 400 mL or 500 mL, and more than 1000 mL was less common in women who received TA versus placebo or no intervention (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.42 to 0.63, six trials, 1398 women; moderate quality evidence) and (RR 0.40, 95% CI 0.23 to 0.71, six trials, 2093 women; moderate quality evidence), respectively. TA was effective in decreasing the incidence of blood loss greater than 1000 mL in women who had undergone CS (RR 0.43, 95% CI 0.23, 0.78, four trials, 1534 women), but not vaginal birth (RR 0.28, 95% CI 0.06, 1.36, two trials 559 women). The effect of TA on blood loss greater than 500 mL or 400 mL was more pronounced in the group of women having vaginal birth than in women who had CS. Mean blood loss (from delivery until two hours postpartum) was lower in women who received TA versus placebo or no intervention (mean difference MD - 77.79 mL, 95% CI -97.95, -57.64, five trials, 1186 women) and this effect was similar following vaginal birth and CS.
Additional medical interventions (moderate quality evidence) and blood transfusions were less frequent in women receiving TA versus placebo or no interventions. Mild side effects such as nausea, vomiting, dizziness were more common with the use of TA (moderate quality evidence). The effect of TA on maternal mortality, severe morbidity and thromboembolic events is uncertain (low quality evidence).
This review was partially funded by the World Health Organization (WHO).
Protocol (2009) DOI: 10.1002/14651858.CD007872
Original review (2010) DOI: 10.1002/14651858.CD007872.pub2
Review update (2015) DOI: 10.1002/14651858.CD007872.pub3